Reductive stress in cancer immunology and targeted therapy

Reductive stress is characterized by the excessive accumulation of cellular reducing equivalents, leading to the disruption of cellular redox homeostasis and a shift toward a reductive intracellular environment. Immune cells exhibit particularly dynamic redox modulation to adapt to activation and differentiation processes during immune responses, such as tumor recognition and destruction. Unlike their immune counterparts, tumor cells employ a specific metabolic mode for uncontrolled proliferation and survival, which may also lead to a shift in the intracellular redox balance. While extensive research has focused on oxidative stress during the immune response and cancer treatment, studies on reductive stress are still in their infancy. This review summarizes the generation process of reductive stress and its impact on cellular function, detailing its mechanisms in immune cells and various cancers, as well as its relevance to cancer treatment. The aim of this study is to explore new avenues for cancer immunotherapy from the perspective of reductive stress.